Our studies are directed to understand the mechanism of action of aflatoxins, the role of metabolism in aflatoxin toxicity and carcinogenesis and how the biological effects produced by these hepatoxins are modulated by genetic, nutritional, hormonal and environmental factors. Specifically, studies are being carried out on (a) the in vivo and in vitro metabolism of aflatoxin B1 to other less potent derivatives and to those derivatives that alkylate DNA and other macromolecules, (b) the enzymes involved in the metabolism of aflatoxin B1 via various pathways, and (c) genetic regulation of the enzymes involved in the metabolism of aflatoxin B1 via various pathways, and (c) genetic regulation of the enzymes involved in the activation and detoxification of AFB1. To achieve some of these objectives we have studied the effect of sex difference on in vivo and in vitro metabolism of AFB1 and found a close correlation between in vivo and in vitro metabolism and aflatoxin, toxicity and carcinogenesis; we have studied the nuclear and microsomal metabolism of AFB1, genetic regulation of this metabolism and the effects of inducers and inhibitors, we have also compared the DNA-alkylating activity of various aflatoxins and metabolites of aflatoxin B1 with their mutagenic and carcinogenic activities and found a good correlation among these parameters. BIBLIOGRAPHIC REFERENCES: Gurtoo, H.L., Motycka, L.E. and Parker (Bejba), N., Sex Dependence of the Metabolic Activation In Vitro of the Mycohepatocarcinogen Aflatoxin B1. J. Medicine 7:1-12, 1976. Gurtoo, H.L., Sex Differences in the Metabolism and Metabolic Activation of Aflatoxin B1 (AFB1) by Rat Hepatic Microsomes, Federation Proceedings, 35(3):330, 1976.